Effects of isoflavones on breast tissue and the thyroid hormone system in humans: a comprehensive safety evaluation.

Isoflavones are secondary plant constituents of certain foods and feeds such as soy, linseeds, and red clover. Furthermore, isoflavone-containing preparations are marketed as food supplements and so-called dietary food for special medical purposes to alleviate health complaints of peri- and postmenopausal women. Based on the bioactivity of isoflavones, especially their hormonal properties, there is an ongoing discussion regarding their potential adverse effects on human health. This review evaluates and summarises the evidence from interventional and observational studies addressing potential unintended effects of isoflavones on the female breast in healthy women as well as in breast cancer patients and on the thyroid hormone system. In addition, evidence from animal and in vitro studies considered relevant in this context was taken into account along with their strengths and limitations. Key factors influencing the biological effects of isoflavones, e.g., bioavailability, plasma and tissue concentrations, metabolism, temporality (pre- vs. postmenopausal women), and duration of isoflavone exposure, were also addressed. Final conclusions on the safety of isoflavones are guided by the aim of precautionary consumer protection.

Prenatal diagnosis of trisomy 20 by chorionic villus sampling (CVS): a case report with long-term outcome.

A case of prenatally diagnosed non-mosaic trisomy 20 in cells cultured from a chorionic villus sample (CVS)is presented. The term placental karyotype was also non-mosaic trisomy 20. The karyotype of the newborn was 46,XY/47,XY,+20 in foreskin cultures and in a second skin culture; blood lymphocyte culture was 46,XY. Aside from diffuse, hypopigmentary swirls along the lines of Blaschko observed on his extremities and trunk, referred to as hypomelanosis of Ito, the patient is clinically normal at 8 3/4 years of age. In addition, he is one of the oldest reported cases of mosaic trisomy 20 confirmed after birth for which the clinical outcome has been monitored. This case demonstrates that these trisomy 20 findings are compatible with normal psychomotor development and phenotype.

The Center for Advanced Nursing Practice evidence-based practice model: promoting the scholarship of practice.

The Center for Advanced Nursing Practice Evidence-Based Practice Model was developed for nurses engaged in clinical practice. It is a practice model, unifying various disciplines for best practice across settings in the care continuum. Each phase of the model's development is described in the manner in which it was used to guide a group of clinical nurse specialists. Clinical applications, ranging from systems- and organization-wide to unit- and population-specific initiatives are presented as selected articles following in this issue to support the efficacy of the model. Conceptually, the model engenders the heart of the practice and has made a difference in shaping the way clinicians think and the way they practice, individually and collectively. In turn, it has promoted the scholarship of practice in the care continuum across treatment settings.

Peripherally inserted central catheter program.

The peripherally inserted central catheter (PICC) is a safe and less costly option to centrally inserted, tunneled, or implanted central vascular access devices. Support for PICC services and reports of results vary among organizations. A comprehensive PICC Program, guided by the Center for Advanced Nursing Practice's Evidence-Based Practice Model, was designed and implemented with successful outcomes. Key program components include administrative, education, clinical practice, and data monitoring to enhance best practice.

Hospital-wide intravenous initiative.

During a 6-month period under the leadership of a clinical nurse specialist, a Midwestern tertiary care hospital explored the need for standardizing a hospital-wide intravenous infusion system, based on best practice. The Center for Advanced Nursing Practice's Evidence-Based Practice Model guided the process for successful design, implementation, and reporting of results. The new system contributed to positive outcomes identified in project goals: (1) to minimize patient risk from interruption of intravenous lines; (2) to increase clinician satisfaction by improved user safety and system standardization; and (3) to demonstrate responsible organizational financial stewardship. Ultimately, the standardized hospital-wide intravenous initiative empowered bedside clinicians by providing an infrastructure for best practice.

Guided imagery: replication study using coronary artery bypass graft patients.

Replication of a guided imagery study, based on the work of D. Tusek and colleagues, was initiated for coronary artery bypass graft patients, using the Center for Advanced Nursing Practice's Evidence-Based Practice Model. Through the leadership of clinical nurse specialists and the support of perioperative and postoperative bedside clinicians, this initiative offered benefits to patients and served as a template for program expansion to other patient populations.

Partial trisomy 20p: familial occurrence.

Partial trisomy 20p syndrome in an uncle and niece are compared to 32 previous cases.

Karyotype studies in 18 ependymomas with literature review of 107 cases.

Cytogenetic studies from 17 pediatric ependymomas and 1 ependymoblastoma are presented. Eight tumors had abnormal karyotypes. Another 107 published cases of cytogenetic analyses from pediatric and adult ependymomas or ependymoblastomas were reviewed. Of the total 125 tumors, 83 (66%) had abnormal karyotypes, of which 24 had a sole autosomal abnormality. Approximately one third had monosomy 22 (-22) or breakpoint 22q11-13, with a higher incidence in adult (56%) versus pediatric (28%) tumors. Structural abnormalities of chromosomes 1, 6, and 17, and numerical abnormalities of 7, 9, 12, and 20, in particular, are also discussed. Although no primary cytogenetic abnormality is evident, these findings may provide direction for additional investigations regarding the classification of these tumors.

Third report of t(19q)(13.4) in mesenchymal hamartoma of liver with comments on link to embryonal sarcoma.

We report the third known case of mesenchymal hamartoma of the liver (MHL) with a balanced translocation involving a common breakpoint, 19q13.4. A common clonal chromosome abnormality appears to characterize an important subset of MHL, some of which may be low-grade neoplasms. We found no consistent karyotype abnormality in a post-treatment sample of embryonal sarcoma of the liver (ESL). Reports of coexistent MHL and ESL in two patients and detection of 19q abnormalities in two ESLs appear to support Stocker's hypothesis of a histogenetic link between these two rare liver lesions. More data are needed to clarify this relationship. It is possible that MHLs are etiologically heterogenous and may be developmental disorders, disruptions, or neoplasms.

Chromosome analyses in a rhabdoid tumor of the brain.

A malignant rhabdoid tumor of the brain from a 19-month-old child was studied. Two related clones, 46,XX,-8,+der(8)t(8;22)(p11;q?12)x2,-22,del(22)(q12q?13) and 46,XX-8,+der(8)t(8;22) (p11;q?12) x2,-22,r(22) were found after chromosome analyses of primary and recurrent tumor, and multiple nude mouse passages of the tumor. Breakpoints were studied using FISH.

Hepatoblastoma in a child with trisomy 18: cytogenetics, liver anomalies, and literature review.

A 26-month-old female with trisomy 18 and repaired omphalocele died of metastatic disease after resection of hepatoblastoma (HB) at 21 months of age. Four other cases (three of them published) suggest that the association of trisomy 18 and HB may be nonrandom. Karyotype abnormalities of the tumor in our case included duplication of 2q and +20, reported previously in HB arising in patients with normal karyotype. Antecedent growth disturbance of liver, either intrinsic (abnormal lobation) or related to contiguous extrinsic anomalies such as omphalocele or local diaphragmatic hypoplasia and possibly augmented by unusual sensitivity to noxious environmental agents, may predispose to hepatoblastoma in trisomy 18. Longevity in trisomy 18 predisposes to both hepatoblastoma and Wilms tumor, possibly by a shared pathway.

Familial partial duplication (1)(p21p31).

A partial duplication (1)(p21p31), resulting from a maternal direct insertion (13,1) (q22p21p31), was found in a 30-year-old woman with mental retardation, cleft palate, and multiple minor anomalies. Two other affected and deceased relatives were presumed to have the same chromosome imbalance. Duplication 1p cases are reviewed.

Supernumerary chromosome marker (1) in a developmentally delayed child.

A 15-month-old boy with mild developmental delay and several minor anomalies was found to be mosaic 46,XY/47,XY ,+mar(1). The marker r(1) was a small de novo ring identified by FISH with a painting type DNA probe.

Cytogenetic and molecular studies of Down syndrome individuals with leukemia.

There is an increased risk of leukemia in Down syndrome (DS) patients, with estimates ranging from 14 to 30 times the incidence rate observed for chromosomally normal children. Furthermore, one type of leukemia, called "transient leukemia" (TL), occurs almost exclusively in DS infants. The basis of the association between DS and leukemia is unknown, but we and others have hypothesized that it may be influenced by the mechanism of origin of the extra chromosome. Therefore, we initiated a cytogenetic and molecular study of nondisjunction in leukemia DS individuals. To date, we have obtained blood and/or tissue samples from 55 individuals consisting of 17 cases with TL, 7 cases of acute nonlymphocytic leukemia subtype M7 (ANLL-M7, or acute megakaryoblastic leukemia, postulated to be related to TL), and 31 cases of other forms of leukemia. Analysis of these cases suggests differences between DS children with TL and those with other types of leukemia or DS individuals with no history of leukemia. Specifically, the TL and ANLL-M7 cases have a highly significant increase in the frequency of "atypical" constitutional karyotypes (i.e., mosaic trisomies, rings, and/or isochromosomes) and are almost always male. Additionally, genetic mapping studies suggest an increase in the frequency of disomic homozygosity, especially in proximal 21q, in DS individuals with TL and ANLL-M7.

Marker chromosome 21 identified by microdissection and FISH.

A child without Down syndrome but with developmental delay, short stature, and autistic behavior was found to be mosaic 46,XX/47,XX,+mar(21) de novo. The marker was a small ring or dot-like chromosome. Microdissection of the marker was performed. The dissected fragments were biotinylated with sequence-independent PCR as a probe pool for fluorescence in situ hybridization (FISH). FISH results suggested an acrocentric origin of the marker. Subsequent FISH with alpha-satellite DNA probes for acrocentric chromosomes, and chromosome-specific 21 and 22 painting probes confirmed its origin from chromosome 21.

Physical mapping of the uterine leiomyoma t(12;14)(q13-15;q24.1) breakpoint on chromosome 14 between SPTB and D14S77.

Uterine leiomyoma is the most common tumor of smooth muscle cell origin and is often associated with the recurrent balanced translocation t(12;14)(q13-15;q24). As an initial step toward finding the gene or genes that are interrupted by the translocation breakpoint, a somatic cell hybrid carrying the derivative 14 as the single t(12;14) translocated chromosome was constructed from a leiomyoma cell line with this translocation. Sequence tagged sites (STS) whose locations on the genetic map of chromosome 14 were known were used to map the breakpoint in the translocated chromosomes. The results of this analysis place the translocation breakpoint on the long arm of chromosome 14 between the proximal marker SPTB and the distal marker D14S77, narrowing the chromosomal translocation breakpoint to a region of approximately 7 cM. The identification of flanking markers on chromosome 14 lays the foundation for efforts to clone the breakpoint and to identify the genes involved in the formation of leiomyoma.

Deletion of (11)(q24.2) in a mother and daughter with similar phenotypes.

A del(11) (q24.2) was ascertained in a 2-year-old child and subsequently in her 20-year-old mother. Both mother and daughter had developmental delay, short stature, and "coarse" facial appearance. We compare our patients' manifestations to those associated with the distal 11q2 deletion phenotype ("Jacobsen" syndrome), and to the one other reported case of del(11)(q24.2). Our patients did not resemble this latter case, but had some findings in common with Jacobsen syndrome. We present our findings in order to contribute to the information on 11q2 deletions.

Detection of unexpected clones of monosomy 7 in childhood acute lymphoblastic leukemia using fluorescence in situ hybridization.

The feasibility of a fluorescence in situ hybridization (FISH) technique for the detection of leukemic clones with masked chromosomal aberration in interphase nuclei was tested in childhood acute lymphoblastic leukemia (ALL). Twenty-one cases of ALL previously studied by classical metaphase cytogenetics were retrospectively analysed using a centromere-specific chromosome 7 probe. Five cases with karyotypic abnormalities of chromosome 7 (2 with trisomy 7, 2 with monosomy 7 and 1 with trisomy & tetrasomy 7) showed a correlation with FISH results, whereas in five other cases monosomy 7 was found in 12-43% of cells only by FISH. The unexpected detection of monosomy 7 in these latter ALL patients suggests that either these clones are quiescent or unable to enter mitosis in vitro. This suggests that FISH and metaphase cytogenetics must be combined whenever possible to obtain comprehensive karyotypic information.